Detailed analysis of the selection process in serial co-infections of cell cultures by wild type Autographa californica nuclear polyhedrosis virus, AcNPV/E2, and Ac360-beta-gal, a genetically engineered strain, shows that the unaltered strain was clearly dominant even when it began as the minority component in the inoculum. A method of calculating a selection coefficient that quantifies the relative advantage of one strain of virus over the other under specific culture conditions is described. Calculated selection coefficients were relatively homogeneous and almost exclusively favored the progenitor. Selection pressure was uninfluenced by the relative proportions of the two strains in the population. Unexpected high frequencies of mixed phenotype plaques were observed during infectivity titrations of media from early serial passages of coinfected cultures. Statistical evaluation implicates some nonheritable combinational phenomenon. Virus plated from mixed phenotype plaques show high segregation of phenotypes implying that genetic recombination does not contribute in a major way to the high mixed phenotype frequencies.