Twenty-four patients with mild-to-moderate hypertension (19 women, 5 men; mean age of 49 +/- 9.1 years) completed a 2-week washout phase followed by 1 week of single-blind placebo. Patients were then given isradipine at 2.5 mg twice daily, which was increased to up to 7.5 mg twice daily according to the blood pressure response, over a 12-month period. Thirteen patients completed the trial. The supine and sitting blood pressure decreased to normal levels within 6 weeks of starting active treatment. Heart rate remained unchanged. Plasma cholesterol and triglycerides did not change significantly. Plasma high-density lipoprotein (HDL) cholesterol increased significantly (p < 0.05) and a decrease (NS) was observed in low-density lipoprotein (LDL) cholesterol and in the LDL/HDL cholesterol ratio. Very-low-density lipoprotein (VLDL) cholesterol did not change, nor did other biochemical laboratory tests, or electrocardiographic and echocardiographic parameters. The most notable side effects were headache (n = 1), flushing (n = 1), palpitations (n = 3), and pretibial edema (n = 1). In conclusion, our results indicate that isradipine is safe and effective in the long-term treatment of mild-to-moderate hypertension. It also appears to have beneficial effects on lipid metabolism.