A case-control study was conducted to investigate the etiology of hairy cell leukemia. Forty-five individuals with histologically confirmed hairy cell leukemia comprised the cases. Three neighborhood controls were selected on the basis of age (+/- 5 years), race, sex, and residence at the time of the interview for each case. There was no association found for cigarette smoking, alcohol or coffee consumption and hairy cell leukemia. With respect to occupational risk factors, employment in woodworking or in farming was of borderline significance. Reported exposure to organic chemicals in the workplace was significantly greater among both sexes of the cases than among their respective matched controls (relative risk (RR) = 3.10). Other variables found to be significantly associated with hairy cell leukemia were farm birthplace (RR = 4.20), anemia (RR = 4.29), migraine (RR = 4.80), infectious mononucleosis (RR = 9.00), and routine use of aspirin (RR = 3.41) or tranquilizers (RR = 4.50). No association between radiation and hairy cell leukemia was detected.