Magnesium deficiency is generally associated with an impaired ability to dispose of glucose. In order to test whether or not increasing the peripheral free Mg concentration ([Mg(2+)]) would enhance glucose disposal, we have carried out glucose infusions in sheep with and without simultaneous infusion of Mg. Basal plasma glucose levels were higher in lactating sheep ('lactators') than in non-lactating sheep (controls) (P < 0.05). The glucose disposal rate (K(G)) with no added Mg was greater in lactators than controls (P < 0.05). When Mg was added to the infusate, K(G) in lactators was reduced (P < 0.005). Infusion of Mg depressed basal insulin levels in controls and lactators (P < 0.0001 for both). The insulin response to the intravenous glucose tolerance test (IVGTT) was lower in lactators compared with controls (P < 0.0001); however, after correcting for the reduced basal insulin level when Mg was included during the IVGTT, there was no difference between the two groups. We conclude that intravenous Mg at the doses used in this study leads to a decrease in basal insulin secretion, and that increasing serum [Mg(2+)] reduces glucose disposal in lactating sheep. Experimental Physiology (2003) 88.4, 533-540.