The sexual transmission of zidovudine-resistant human immunodeficiency virus type 1 (HIV-1) variants was investigated in 5 donor-recipient pairs in which all donors and none of the recipients had received zidovudine treatment. The virus isolates were tested for sensitivity to zidovudine (IC50) in vitro using blood donor lymphocytes. A region of the HIV-1 pol gene was also directly sequenced by a solid-phase sequencing method. Four donors were shown to have zidovudine-resistant HIV-1 variants. Two of these patients had a single mutation (Thr215-->Tyr), and 2 had a double mutation (Met41-->Leu and Thr215-->Tyr) that previously has been shown to confer zidovudine resistance. Zidovudine-resistant virus was found in only 1 of the 4 recipients, which indicates that zidovudine-resistant HIV-1 variants may be selected against during transmission. Thus, the transmission of zidovudine-resistant HIV-1 variants is a complex process that will require consideration whenever zidovudine treatment is initiated in persons who may have been infected by resistant variants.