Fertilizer use remains very low in most of Africa despite widespread agreement that much higher use rates are required for sustained agricultural productivity growth. This study uses longitudinal farm survey data to estimate maize yield response functions in a relatively high-potential zone of Zambia to determine the profitability of fertilizer use under a range of small-farm conditions found within this zone. The theoretical framework used in this study incorporates agronomic principles of the crop growth process. We generalize the asymmetric production models and define a concept of yield scaling factors. The model distinguishes different roles of inputs and non-input factors in crop production. We estimate the effects of conventional production inputs as well as of household characteristics and government programs on maize yield. The results indicate that recommended fertilizer application rates in the two specific years were often unprofitable, given observed price conditions and the yield response to fertilizer. However, there was substantial variability in yield response to fertilizer based upon the rate of application, the timeliness of fertilizer availability, the use of animal draught power during land preparation, and whether the household incurred the death of an adult member in the past three years. These modifying factors, as well as variations in input and output prices due to proximity to roads and markets, substantially affected the profitability of fertilizer use on maize.