The aim of the present study was to evaluate whether alterations of leukocyte aggregation are present before the development of smoking-associated diseases. Leukocyte aggregation, studied by means of the leukergy test, was significantly higher in 24 healthy smokers as compared to 18 healthy non-smokers (mean + SE) 4.4 +/- 2.2 vs 1.5 +/- 1.3; P < 0.02. Intermediate values were found in ex-smokers. A significant increase was observed in smokers who underwent the acute smoking of three cigarettes in 20 minutes (mean +/- SE) 3.5 +/- 1.9 vs 7.5 +/- 2.6; P < 0.02. These data indicate that changes of leukocyte aggregation induced by smoking are present in healthy subjects before the development of clinically evident diseases associated with smoking.