Seventy-four HIV-infected homosexual males belonging to CDC groups IIB, III, and IVC2 were treated with increasing doses of zidovudine within the Multicentre Canadian AZT Trial. Following a 3 week observation period, consenting volunteers received 600 mg/day for 18 weeks, 900 mg/day for 9 weeks, and 1,200 mg/day for 9 weeks. This was followed by a 6 week washout period after which zidovudine was restarted at 1,200 mg/day for 18 weeks. Patients were followed for a total of 63 weeks. Every 3 weeks they underwent a full clinical and laboratory assessment. For the purpose of this analysis, subjects were divided according to the mean initial platelet value (greater than or equal to 150,000 or less than 150,000/L) into normals (n = 57) and thrombocytopenics (n = 12), respectively. Analysis of variance was used to compare the mean platelet values at each zidovudine dose. All comparisons were made against baseline values. Zidovudine increased platelet counts in normal and thrombocytopenic subjects. The magnitude of this effect varied depending on the baseline platelet count. Among normals, the platelet count increased from 241,000 +/- 45,000/L at baseline to 261,000 +/- 51,000/L (p less than 0.01). while receiving 600 mg/day of zidovudine. This effect was self-limited, reaching a peak by week 3. The platelet count decreased to baseline values despite increasing the dose of zidovudine to 900 or 1,200 mg/day. The platelet count further decreased to 218,000 +/- 43,000/L during the washout phase (washout vs. 1,200 mg, p less than 0.01).2+ not found to be dose related. The platelet count decreased to 101,000 +/- 34,000/L during the washout phase (washout vs. 1,200 mg/day, p less than 0.07).(ABSTRACT TRUNCATED AT 250 WORDS)