This study was conducted to evaluate the in vivo genotoxicity of zidovudine (ZDV) in patients with Acquired Immune Deficiency Syndrome (AIDS). Patients with this disease who were non-smokers and on ZDV (1200 mg/day) as their only medication for 4 weeks to 7 months were studied. Patients with AIDS who had not received ZDV served as a negative control. Whole blood cultures were initiated by conventional methods with PHA 1:50 dilution. In addition, for each culture there was an untreated control and a recombinant interferon-beta (rIFN-beta)-treated culture. The IFN-treated cultures were exposed to 10, 100, 1000, or 10000 units of rIFN-beta for the entire incubation period. The cells were harvested at 72 h and stained with a fluorescence plus Giemsa method which permits the determination of the number of division cycles a cell has completed. One hundred metaphases from first division cells were scored from each culture for chromosome aberrations that were mainly from the chromatid-type, i.e. chromatid, chromosome, and isochromatid breaks. The frequency of breaks in the ZDV and no ZDV group was 8.29 +/- 2.65 and 0.5 +/- 0.29 per 100 cells respectively (P less than 0.05). Cultures from ZDV patients that were incubated with 100 and 1000 units of rIFN-beta, however, showed a frequency of 1.3 +/- 0.71 and 1.9 +/- 1.08 respectively, which was significantly lower than observed in the cultures not exposed to IFN (P less than 0.05). At the highest dose of rIFN-beta utilized no aberrations were detected.(ABSTRACT TRUNCATED AT 250 WORDS)