Two densities, two temperatures and three genotypic compositions were used to study selection in cultures of Drosophila polymorphic for Est-6. The alleles used were the common Est6 s and Est6 VF which has a frequency of about 0.03 in Italian natural populations. Significant effects of all variables on viability were seen and interaction of both the environmental variables with genotypic composition occurs. While frequency-dependent selection is demonstrated in many combinations it is least evident at the genotypic composition (pVF = 0.2) closest to that found in nature where heterotic selection appears to be important. The significance of these findings for the maintenance of the polymorphism in nature is briefly discussed.