We have studied the effects of chronic treatment with cromakalim (75 ug kg(-1) per day) and glibenclamide (20 mg kg(-1) per day) in alloxan-induced diabetic rats. Injection of alloxan (60 mg kg(-1)/i.v., single dose) produced a significant increase in the blood pressure, bradycardia, hyperglycemia, hypoinsulinemia, hyperlipidemia, hypothyroidism and depression in left ventricular developed pressure (LVDP). While glibenclamide significantly prevented alloxan-induced hyperglycemia and hypoinsulinaemia, it failed to alter hypertension, bradycardia, hypertriglyceridaemia and hypercholesterolemia. Treatment with cromakalim-prevented hypertension and bradycardia, but not the hyperglycemia or hypoinsulinaemia. Co-administration of cromakalim with glibenclamide antagonized the effect of glibenclamide on these parameters. Cromakalim treatment also prevented alloxan-induced hypercholesterolemia and hypertriglyceridaemia. It also produced a significant increase in serum T(3) and T(4) levels. Glibenclamide did not significantly alter alloxan-induced hypothyroidism. In conclusion our data suggest that cromakalim and glibenclamide produce some metabolic effects that are either not related to K(ATP) channel modulation or may involve different sub-types of potassium channels. Further glibenclamide when combined with cromakalim may not be beneficial in a condition when diabetes mellitus and hypertension co-exits.