Including open alleys at ends of plots is a common practice when field-testing foliar fungicides used in corn production. Open alleys facilitate movement of workers and equipment between plots during spray application. Open alleys affect crop yield estimates in small plots typically used in replicated, randomized experimental designs, because of reduced interplant competition. However, no published research has tested whether the alley effect interacts with fungicide to bias the assessment of the agronomic effects of the latter. We tested this hypothesis over 2 years by evaluating yield with and without application of Headline AMP (containing pyraclostrobin and metconazole) plus nonionic surfactant applied once at VT/R1 in 7.6-m plots separated on their ends by 1.5-m alleys free of aboveground vegetation. In each plot, data were collected from seven subplots, each measuring 1.09 m of row-length and running parallel to the long axis of the plot. Consistent with previous reports, yields of subplots were substantially higher toward plot ends than in the central areas of plots. Surprisingly, a significant (P < 0.10) fungicide × subplot interaction was observed in both experiments, indicating that the yield response from fungicide depended on subplot position within the plot. However, yield differences due to fungicide were trivial when comparing regression-based yield estimates from all seven subplot positions to those obtained from only the centermost three subplot positions. Our study does not lend support to the hypothesis that the open-alley design creates a meaningful bias in assessment of treatment effects due to foliar fungicides in corn. However, additional research on this question is warranted, given the complexities of comparing results in large-scale plots vs. small plots, the limitations of our study, and the widespread use of fungicides on field corn in the United States.