OBJECTIVE To evaluate the effects of isradipine alone and in combination with pindolol on glucose and lipid metabolism during long-term antihypertensive therapy. METHODS Open long-term study with parallel groups. METHODS Kungsgärdet Geriatric Hospital, Uppsala, a tertiary referral hospital. METHODS Twenty-six untreated hypertensive subjects. METHODS After 4 weeks on placebo, isradipine was titrated up to 10 mg daily to achieve appropriate blood pressure control (n = 11). If this failed, 5-10 mg pindolol was added. The treatments were continued for 2 years. METHODS Blood pressure, lipoprotein measurements, intravenous glucose tolerance test, hyperinsulinaemic euglycaemic clamp, HbA1c, body weight. RESULTS Treatment with isradipine alone caused a sustained reduction in blood pressure (-22/-10 mm Hg, P < 0.01), but an increase in body weight (+2.2 kg, P < 0.05) and HbA1c (+1.5%; P < 0.001) were also noted. Addition of pindolol resulted in a similar degree of blood pressure reduction and weight gain, whilst HbA1c was less affected (+1.0%; P < 0.05, compared to isradipine alone). Insulin sensitivity became impaired in both groups (-1.2 to -1.5 mg kg-1 min-1; P < 0.01 for M-value at hyperinsulinaemic clamp) but after adjustment for the change in body weight the impairment was only significant (P < 0.01) in the group with combined treatment. The combined treatment also resulted in an increase in very-low-density-lipoprotein (VLDL) triglycerides (+ 0.37 mmol L-1; P < 0.05). CONCLUSIONS The hypotensive effect of isradipine was sustained during long-term use but was associated with weight gain and an impaired glucose control. When isradipine was combined with pindolol there was also a reduction in insulin sensitivity and an increase in VLDL triglycerides, possibly as effects of the beta-adrenergic blockade.