Twenty-four specific pathogen-free kittens were infected with the Rickard strain of feline leukemia virus (FeLVR). The kittens were divided into four equal groups and were orally administered either a high dose of diethylcarbamazine (DECH, 12 mg kg-1), a low dose of diethylcarbamazine (DECL, 3 mg kg-1), 3'-azido-3'-deoxythymidine (AZT, 15 mg kg-1, b.i.d.), or a placebo (250 mg granular dextrose) daily for 10 weeks. Blood was collected at 2-week intervals for complete blood counts (CBC) and flow cytometric analysis (FACS) of peripheral blood lymphocytes (PBL). Plasma was assayed for antibodies to FeLV gp70 and for FeLV p27 antigen using ELISA assays. For FACS analysis, lymphocytes were incubated with monoclonal antibodies to feline Pan T, CD8+, CD4+, and B cell (Anti-Ig) antigens. In the placebo treated cats, FeLVR infection caused an early (2 weeks p.i.) and persistent decrease in leukocyte numbers attributable primarily to a decrease in neutrophil numbers and a secondary lesser decrease in B and CD4+ lymphocyte numbers. The DEC-treated groups showed a delayed but similar leukopenia by 4 weeks p.i. The lymphopenia in the DEC groups (primarily B cells and CD4+ cells) was reversed by 10 weeks p.i., but the neutropenia persisted. AZT treatment inhibited FeLVR-induced lymphopenia but did not prevent a reduction in neutrophil numbers. A marked p27 antigenemia that peaked at 4 weeks p.i. was noted in the placebo treated cats and in most cats (11/12) treated with either dose of DEC. However, AZT significantly inhibited the p27 antigenemia and all cats were negative for p27 antigen between 6 and 10 weeks of treatment. In general, placebo treated cats as well as DECH and DECL cats had low levels of antibody to gp70 throughout the study, suggesting FeLVR-induced immunosuppression. In contrast, significantly higher titers of anti-gp70 antibodies were seen in AZT-treated cats at 6 weeks p.i., and were maintained throughout treatment. Eighteen month survival rates provide efficacy data for AZT as well as both DEC treatment groups. While all placebo treated cats were euthanized by 52 weeks p.i. due to FeLV associated lymphomas with a mean survival time of 35.5 weeks p.i., median survival time of the AZT treated group was > or = 102 weeks p.i., while that of the DECH and DECL groups was 69.7 and 72 weeks p.i., respectively. Thus, DEC as well as AZT therapy delays the development of lymphomas associated with FeLV infection and significantly improves survival.