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Long-term applications of inorganic fertilizers and farmyard manure influence organic matter as well as other soil-quality parameters, but the magnitude of change depends on soil-climatic conditions. Effects of 22 annual applications (1982-2003) of N, P, and K inorganic fertilizers and farmyard manure (M) on total organic carbon (TOC) and nitrogen (TON), light-fraction organic C (LFOC) and N (LFON), microbial-biomass C (MB-C) and N (MB-N), total and extractable P, total and exchangeable K, and pH in 0-20cm soil, nitrate-N (NO3--N) in 0-210 cm soil, and N, P, and K balance sheets were determined using a field experiment established in 1982 on a calcareous desert soil (Orthic Anthrosol) at Zhangye, Gansu, China. A rotation of irrigated wheat (Triticum aestivum L.)-wheat-corn (Zea mays L.) was used to compare the control, N, NP, NPK, M, MN, MNP, and MNPK treatments. Annual additions of inorganic fertilizers for 22 y increased mass of LFON, MB-N, total P, extractable P, and exchangeable K in topsoil. This effect was generally enhanced with manure application. Application of manure also increased mass of TOC and MB-C in soil, and tended to increase LFOC, TON, and MB-N. There was no noticeable effect of fertilizer and manure application on soil pH. There was a close relationship between some soil-quality parameters and the amount of C or N in straw that was returned to the soil. The N fertilizer alone resulted in accumulation of large amounts of NO3--N at the 0-210 cm soil depth, accounting for 6% of the total applied N, but had the lowest recovery of applied N in the crop (34%). Manure alone resulted in higher NO3--N in the soil profile compared with the control, and the MN treatment had the highest amount of NO3--N in the soil profile. Application of N in combination with P and/or K fertilizers in both manured and unmanured treatments usually reduced NO3--N accumulation in the soil profile compared with N alone and increased the N recovery in the crop as much as 66%. The N that was unaccounted for, as a percentage of applied N, was highest in the N-alone treatment (60%) and lowest in the NPK treatment (30%). In the manure + chemical fertilizer treatments, the unaccounted N ranged from 35% to 43%. Long-term P fertilization resulted in accumulation of extractable P in the surface soil. Compared to the control, the amount of P in soil-plant system was surplus in plots that received P as fertilizer and/or manure and the unaccounted P as percentage of applied P ranged from 64% to 80%. In the no-manure plots, the unaccounted P decreased from 72% in NP to 64% in NPK treatment from increased 13 uptake due to balanced fertilization. Compared to the control, the amount of K in soil-plant system was deficit in NPK treatment, Le., the recovery of K in soil + plant was more than the amount of applied K. In manure treatments, the recovery of applied K in crop increased from 26% in M to 61% in MNPK treatment, but the unaccounted K decreased from 72% in M to 37% in MNPK treatment. The findings indicated that integrated application of N, P, and K fertilizers and manure is an important strategy to maintain or increase soil organic C and N, improve soil fertility, maintain nutrients balance, and minimize damage to the environment, while also improving crop yield.