We studied variations in DLCO during the menstrual cycle in 14 healthy women with a mean age of 29 (SD, 7) yr. Eight were using oral contraceptives, and six were not. DLCO was determined 1 to 7 d before the onset of menses, daily during each of the first 4 d of menses, and 5 to 10 d after onset of menses. In both groups of subjects, the highest values for DLCO were obtained before menses, the lowest were on the third day of menses, whereas after completion of menses the values increased but were not as high as prior to menses. The mean DLCO for all subjects was 23.1 (SD, 3.2) ml/min/mm Hg before menses, 20.9 (SD, 3.0) on the third day of menstruation, and 21.6 (SD, 3.3) 5 to 10 d after onset of menses. The mean percent difference between DLCO before and on the third day of menses in all 14 subjects was 9.2 (SD, 4.4) %. There were no significant changes in hemoglobin on these days to account for the changes in DLCO. Pulmonary capillary blood volume determined in 10 of the subjects did not show a significant change. It is concluded that DLCO can vary significantly during the menstrual cycle, with the highest values occurring prior to menses and the lowest values occurring on the third day of menses, with a mean difference between them of 9%. These variations need to be considered when evaluating DLCO in female patients in the menstrual age group.