We have previously reported that modest dietary sodium restriction, as advocated in management guidelines for diabetes, may reduce insulin sensitivity. It has since been suggested that this effect may be mediated via cross-talk between insulin and angiotensin II (AII)-stimulated intracellular second messengers. In order to assess the effect of 5 days of modest sodium restriction (to <80 mmol/day target sodium intake) on insulin sensitivity, 15 healthy males underwent a double-blind, placebo-controlled, randomized, cross-over euglycaemic hyperinsulinaemic clamp study. One phase was supplemented with sodium tablets and the other with matched placebo. Insulin sensitivity (M) was reduced during dietary sodium restriction [median M value, 10.2 mg/kg per min (interquartile range 9.50-13.85) versus 12.8 mg/kg per min (interquartile range 9.60-14.30), P <0.05]. To elucidate potential mechanisms that may explain this observation, we investigated the effect of AII on insulin action in isolated adipocytes obtained from healthy females. No effect of AII on insulin-mediated glucose transport or suppression of lipolysis was observed. In conclusion, despite the observation that dietary sodium restriction was associated with a median 15% reduction in insulin sensitivity, we found no evidence of a direct effect of AII on insulin action in human adipocytes.