Infection with adeno-associated virus type 5 (AAV-5) reduced the number of mutants arising in the hypoxanthine phosphoribosyltransferase locus of human RD 176 cells after infection with herpes simplex virus type 1 (HSV-1; partially inactivated) or 4-nitroquinoline-1-oxide (4-NQO). The mutation frequency was reduced by AAV-5 infection from 11.4 to 1.8 after mutation with HSV-1 and from 3.2 to 2.5 when mutation was induced by 4-NQO. This was analyzed by determination of the number of cells resistant to 8-azaguanine when infected with AAV-5 prior to induction of mutations with HSV-1 or 4-NQO.