The clinical significance of an isolated reduction in the carbon monoxide diffusing capacity (DLCO) in nonsmoking, asymptomatic individuals is not known. Whether a reduced DLCO despite otherwise normal pulmonary function tests warrants further investigation remains unanswered. In this article, the authors describe five healthy, asymptomatic, young women who had isolated, reduced DLCO and subsequent follow-up examinations over a span of 6 years. This case series lends support to the contention that an isolated low DLCO in asymptomatic subjects is not clinically significant and does not necessitate additional medical inquiry.