Reports of diverse relationships between blood concentrations of different lipids and peripheral total leukocyte count, and a unique lower peripheral monocyte count in hypercholesterolemia, have driven us to think that in humans, peripheral differential leukocyte counts may be influenced differently by different types of hyperlipidemia. Our subjects were Taipei residents who attended a regular health check program in our hospital in 1998. A total of 3,282 subjects was enrolled, including 1,677 normolipidemic, 960 untreated borderline hyperlipidemic, and 645 untreated hyperlipidemic subjects. By one-way analysis of variance (ANOVA), we found that different types of hyperlipidemia were associated with significant differences in differential leukocyte counts. In hypertriglyceridemia, the total leukocyte count and counts of all leukocyte subtypes were significantly higher than those in normolipidemia. Pure hypercholesterolemia, by contrast, was associated with a significantly lower monocyte count and no significant difference in other leukocyte counts. By two-way ANOVA adjusted for presence and degree of hyperlipidemia, we found significantly higher counts of total leukocytes and of all leukocyte subtypes in smokers, and significantly positive trends in relationships between body mass index (BMI) and counts of all leukocytes, neutrophils, lymphocytes, and monocytes. By multivariate regression analysis including all subjects, the serum triglyceride (TG) level was positively correlated with total leukocyte count and counts of all subtypes except eosinophils. On the contrary, serum high density lipoprotein-cholesterol had a negative correlation with total leukocyte count and with counts of neutrophils, monocytes, and basophils. In these multivariate regression analyses, there was no significant correlation between lipid levels and eosinophil count, whereas smoking was consistently associated with significantly higher counts of all leukocyte subtypes, including eosinophils. BMI had a significantly positive correlation with counts of all leukocytes, neutrophils, lymphocytes, and monocytes.