This study compared the effects of continuous subcutaneous insulin infusion (CSII) and conventional insulin therapy (CIT) on serum lipid and lipoprotein levels in type I diabetic patients during 1 year cross-over study (6 months on CSII and 6 months on CIT). The study group consisted of 28 normolipidemic and nonobese diabetic patients (14 males and 14 females) aged 31 +/- 2 yr. The glycemic control was moderate (HbA1 10.2 +/- 0.3%) before starting the study. During the first 6 months, the HbA1 level fell significantly in the CSII group (from 10.4 +/- 0.5% to 9.8 +/- 0.4%, P less than 0.05), but remained unchanged in patients on CIT. During the second 6 months after cross-over no significant alterations in HbA1 levels were observed in either group. HDL-cholesterol (HDL-chol) rose by 38% during the first 6 months in the patients using CSII (P less than 0.001) and by 18% in the CIT group (P less than 0.005). The rise in HDL-chol was accounted for by an increase in both HDL2-chol and HDL3-chol subfractions. Following the shift from CIT to CSII, HDL2-chol rose further (P less than 0.05), whereas HDL3-chol remained unchanged. When CSII was changed to CIT, the HDL3-chol level decreased (P less than 0.02), but HDL2-chol remained constant. There was no correlation between HDL-cholesterol and HbA1 levels or between the changes in either variable. HDL2-chol was 35% higher in females when compared to males at entry, and it rose in both sexes during CSII. HDL3-chol elevated during CSII only in females. CSII or CIT treatments did not cause significant changes in cholesterol or triglyceride levels of VLDL or LDL lipids during the study. Thus, even a mild improvement in glycemic control during CSII is associated with a rise in HDL-chol, particularly the HDL2 subfraction.