School-based drug-use prevention studies often apply interventions to entire schools. A major problem for these studies results from the intragroup dependence often seen when intact social groups are assigned to study conditions. Analysis of data from 2 such studies revealed intraclass correlation coefficients between 0.02 and 0.05 for common drug use measures. Because even such modest intragroup dependence can invalidate the traditional fixed-effects analyses, researchers should adopt alternative methods that acknowledge this dependence. These alternative methods are reviewed, and appropriate methods for computing sample size requirements are illustrated. Investigators should consider these analysis issues when planning future studies, because the number of schools required for an unbiased analysis may be substantially greater than for the traditional methods.