Retroviruses have a high mutation frequency. However, until recently protocols had not been developed for measuring retroviral mutation rates, that is, the mutation frequency in a single cycle of retrovirus replication. Using a recently developed protocol (Dougherty and Temin, 1986) experiments are proposed to determine retrovirus mutation rates for defined mutations, such as base substitutions, insertions, deletions, and inversions. Experiments measuring recombination mutation rates are also proposed. Mutation rates will be determined using spleen necrosis virus (SNV)-, murine leukemia virus (MLV)-, and human immunodeficiency virus (HIV)-based retroviral vector systems. Studies are also proposed to determine mutation rates using replication-competent retroviruses.