In order to evaluate the effects of atrial natriuretic factor (ANF) infusion on plasma insulin (IRI) in hypertension, 32 essential hypertensives (aged 40 to 62 years) were studied. After 1 week of pharmacologic washout under normal sodium intake (120 mEq of Na+/day), patients were randomly assigned to receive either ANF (0.04 micrograms/kg/min) or its vehicle (50 mL of isotonic saline) over a 60-min period in supine position. Plasma IRI and glucose were measured at -60, 0, 20, 40, 60, 120, 180, and 240 min (infusion time: from 0 to 60 min). Plasma levels of IRI and glucose did not change significantly during ANF infusion. On the contrary, after ANF discontinuation plasma IRI rose from levels of 13.5 +/- 6.4 microU/mL at 60 min to values of 20.1 +/- 11.3 microU/mL at 240 min (P less than .0001 v time 0). Plasma glucose showed a similar behavior, increasing from values of 100.4 +/- 5.0 mg/dL at 60 min to values of 120.0 +/- 5.1 mg/dL at 240 min (P less than .02 v time 0). Our findings suggest that ANF did not influence insulin release in hypertensives. The increase of plasma glucose and IRI observed after ANF discontinuation could be due to the relapse of sympathetic activity, suppressed during ANF infusion.