The acute effect of cigarette smoking on blood leukocyte values in four healthy young women is reported. In a cross-over experiment using the Hemalog-D automated differential system, the effect of smoking four to 12 cigarettes on the time course of the concentration of leukocyte types was studied. During each of two experiments lasting from 800 h to 1400 h, the subjects were in the supine position. Each subject abstained from smoking during one experimental day and started smoking at 930 h on the other experimental day. The values obtained during each experimental day were expressed for each subject as change from the baseline values measured before 930 h. The time course for the lymphocyte concentration changed significantly (P less than 0.05) on the day of smoking as compared with the day of not smoking, showing an initial elevation followed by a more prolonged depression. The eosinophil concentration was uniformly and significantly (P less than 0.05) depressed. The neutrophil concentration showed a delayed response, with an elevation starting at 1200 h. The latter effect, however, was of borderline significance (P = 0.07).