We compared infection rates in 12 patients with hairy cell leukemia (a malignant neoplasm for which the cell of origin remains controversial) with rates in 15 patients with chronic lymphocytic leukemia (a known B-lymphocyte neoplasm) recently treated at four Dallas hospitals. We found a significantly higher over-all rate of infections in the patients with hairy cell leukemia (P = 0.004 BY Gehan's variation on the generalized Wilcoxon test). This increased rate was primarily due to a significantly higher rate of infections normally controlled by the cell-mediated immune system (P = 0.005). Despite these findings, five of six patients with hairy cell leukemia who were skin-tested exhibited intact delayed type hypersensitivity, and each of the three patients examined serologically produced antibodies normally in response to recent infections. A review of the case records of 173 previously described patients with hairy cell leukemia, demonstrated a similar predilection of patients with this disease for infections normally controlled by cell-mediated immunity. In this regard, they were similar to previously described patients with Hodgkin's disease. Both over-all infection rates and rates of fatal infection were highest in patients with hairy cell leukemia who received chemotherapy as their sole form of treatment and lowest in those who underwent splenectomy as their only form of antitumor therapy.