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Multiple intravenous injections of contrast media are used in radiology, but information regarding corresponding changes in the serum iodine concentrations and osmolality is lacking. We measured the changes in serum iodine concentration and serum osmolality in rabbits after a series of intravenous injections of contrast media. Hypaque-76 (1 cc/kg) was injected intravenously in awake rabbits at 10-minute intervals for 1 hour and arterial blood sampled at midpoint times between injections. During the 1-hour period of seven serial injections, mean serum iodine concentration at 5 minutes was 2.3 mg I/cc (± 0.1 SEM, n = 14) at 35 minutes, S.I mg I/cc (± 0.2); and at 65 minutes, 6.7 mg I/cc (± 0.4). The mean peak concentration was 6.8 mg I/cc ( ± 0.4). Serum osmolality underwent a mean increase of 16 mosm/kg during the injection period. Hypertonic mannitol injections produced a smaller increase in osmolality (10 mosm/kg). Isotonic saline injections in control animals produced no change in osmolality.