Magnesium (Mg(2+)) has an important role in insulin action, and insulin stimulates Mg(2+) uptake in insulin-sensitive tissues. Impaired biologic responses to insulin are referred to as insulin resistance. Diabetic patients and obese subjects are reported to have intracellular magnesium ([Mg(2+)](i)) deficiency. Many epidemiologic studies have disclosed that restricted fetal growth has been associated with increased risk of insulin resistance in adult life. We studied the relationship of [Mg(2+)](i) in cord blood platelets to birth weight. The subjects were 19 infants who were small for gestational age (SGA) and 45 who were appropriate for gestational age (AGA). By using a fluorescent probe, mag-fura-2, we examined the basal and insulin-stimulated [Mg(2+)](i) of platelets in the cord blood. Cord plasma insulin-like growth factor-1 (IGF-1)and leptin levels were determined with the use of enzyme-linked immunosorbent assay (ELISA). Birth weight was correlated with cord plasma IGF-1 (P < .001) and leptin (P < .005). Mean basal [Mg(2+)](i), but not plasma Mg(2+), was lower in the SGA than in the AGA group (291 +/- 149 micromol/L v 468 +/- 132 micromol/L, P < .001). The basal [Mg(2+)](i) was significantly correlated with the birth weight (P < .001) as well as birth length (P < .001). At 60 seconds after stimulation with insulin, there was no significant difference in stimulated [Mg(2+)](i) between the SGA and AGA groups. Although the SGA group had low [Mg(2+)](i), the platelets had good potentiality to compensate for low [Mg(2+)](i). [Mg(2+)](i) reflects the extent of fetal growth. Decreased [Mg(2+)](i) in SGA might underlie the initial pathophysiologic events leading to insulin resistance.