The immune function of patients with hairy cell leukemia (HCL) and solid tumors was evaluated before and after treatment with the investigational drug 2'-deoxycoformycin (pentostatin; dCF). Thirteen HCL patients received doses of dCF of 2 to 4 mg/m2 intravenously at 2- to 6-week intervals for up to 15 courses. After completion of treatment, 12 of 13 patients had resolution of severe monocytopenia and five of nine had normal monocyte antibody dependent cellular cytotoxicity. There was statistically significant depression of total lymphocytes, T cells, and B cells. Evaluation of T subsets showed a decrease in CD4+ cells. Immunoglobulin G (IgG) in sera were decreased from baseline, while IgM and IgA were unaffected. There was no significant effect on skin-test reactivity or large granular lymphocyte numbers. Lymphoblastic transformation was variably affected. Natural-killer (NK) cell function was improved or unchanged after dCF treatment. Reevaluation of seven patients at 21 to 119 weeks after receiving dCF demonstrated that recovery to normal T- and B-cell numbers and subsets does occur. Five solid tumor patients were given dCF at 4 mg/m2 intravenously at 1- to 2-week intervals for up to five courses. There was significant reduction in T cells, B cells, CD4+, and CD8+ cells with no statistically significant effect on the other immune parameters. We conclude that low doses of dCF can cause persistent immunosuppression though recovery may occur after the drug is stopped. In patients followed after completion of dCF, there was no associated increase in second malignancies or unusual infections.