In cross-sectional studies, significant differences in cardiovascular disease risk factors have been observed between smokers and non-smokers. The aim of this study was to examine the effects of smoking initiation and cessation on these factors in a population-based prospective study. 987 male employees in Israeli industry underwent health screening in the CORDIS study and were re-examined an average of two and a half years later. We examined the associations between smoking initiation and cessation and changes in blood count, serum lipids and lipoproteins, body weight and blood pressure. After adjusting for potential confounders, smoking cessation was associated with significant decreases in leukocyte count, hemoglobin and hematocrit whereas smoking initiation resulted in increased leukocyte count. There were moderate, non-significant increases in both serum HDL cholesterol (HDL-C) and LDL-C, and a slight decrease in serum triglycerides. Blood pressure remained essentially unchanged, despite the fact that smoking cessation resulted in a significant weight increase and smoking initiation in a significant decline in weight. These findings demonstrate that changes in smoking habits result in fairly rapid changes in blood count and body weight, but have much smaller effects on serum lipids and blood pressure.