Twenty-two smokers with elevated hematocrits (mean, 54 per cent) had elevated blood carboxyhemoglobin (mean, 11.6 per cent; normal, less than 1 per cent) and a "left-shifted" oxygen-hemoglobin dissociation curve (mean P50, 21.6 +/- 2.3 [+/- S.D.] torr; normal, 26.7 +/- 1.1). Red-cell volume was increased in 14 of 18, and plasma volume reduced in 14 of 18. Fatigue and headache were common, and syncopal attacks occurred in four patients. Symptoms disappeared and the elevated red-cell volume decreased markedly in all five patients who were able to reduce severely their smoking habit; low plasma volume increased in three of four patients studied. We conclude that carbon monoxide exposure from cigar and cigarette smoke is a frequent cause of an elevated red-cell volume or a reduced plasma volume (or both). Measurement of carboxyhemoglobin should be a routine part of the evaluation of all polycythemic subjects.