While numerous groups have reported high prevalences of plasma lipid abnormalities in their renal transplant recipients, we have been unable to confirm this finding. We have suggested that the routine use of alternate-day steroids (ADS) in our patients may be responsible. To test that hypothesis, a prospective controlled trial of equal total dose ADS versus daily steroids (DS) was conducted. Four months after transplant and before entering the trial, transplant study patients had significantly higher serum cholesterol (243 +/- 9 mg/dl) than either normal controls (cholesterol 200 +/- 7 mg/dl, alpha = 0.01) or hemodialysis patients (cholesterol 211 +/- 9 mg/dl, alpha = 0.01). They also had higher serum triglyceride than controls (129 +/- 7 mg/dl vs. 98 +/- 8 mg/dl, alpha = 0.01). After randomization to DS or ADS and 1 year of further followup study, the ADS group had a significant decrease in both serum triglyceride (139 +/- 9 to 100 +/- 7 mg/dl, P less than 0.01) and cholesterol (251 +/- 16 to 220 +/- 9 mg/dl, P less than 0.05) while the DS group's serum triglyceride and cholesterol values remained unchanged. Serum triglyceride and cholesterol in the ADS group had decreased to values that were not significantly different from 41 normal healthy controls. Dose spacing per se, and not the use of a lower total dose of prednisone, appears to result in a lower prevalence of abnormal plasma lipids after successful renal transplantation.