Replicate D. pseudoobscura lines from populations collected at different geographic locations were selected for increased knockdown resistance to ethanol. Population background affected the initial rate of response but not the extent that lines responded. Lines were tested for physiological traits contributing to increased knockdown resistance. Populations showed different correlated responses for two traits (tolerance of ethanol, and of acetone), suggesting that they had responded to selection by different mechanisms. Replicate lines had diverged for most traits. The results indicate that drift and/or differences in genetic background can lead to divergence under uniform selection, even when fairly large population sizes are maintained.