A form of G-->A hypermutation preferentially affecting GA dinucleotides of genomic RNA has been found to occur in retroviral systems ("type 1"). In a detailed longitudinal study of an AIDS patient we have observed a new type of G-->A hypermutation, which preferentially affects one or more 5' G residues in runs of G's. HIV-1 proviral DNA samples obtained at widely separate times during this patient's course contained representatives of this type of G-->A hypermutation, designated "type 2." We propose that G-->A hypermutation is caused by a mutated form of the HIV-1 reverse transcriptase; and that hypermutated DNA may persist for long periods in infected patients, perhaps as proviral DNA in long-lived cell lineages. Like type 1 G-->A hypermutation, type 2 G-->A hypermutation may contribute to the heterogeneity of replicating pools of HIV by recombination.