Plasma clearance of iohexol was evaluated in eight anesthetized California sea lions (Zalophus californianus), without evidence of renal dysfunction, to determine if the one-compartment model and the sample protocol used in dogs and cats could be applied to this species. Nonlinearity between samples in 75% (6/8) of sea lions voided those results. An additional two anesthetized sea lions were sampled at 5, 30, 45, 60, 120, 180, 240, and 360 min post iohexol injection and semi-logarithmic curves calculated. Plasma iohexol clearance values calculated by one-, two-, and noncompartment models were in poor agreement, suggesting that the standardized protocol described for dogs and cats cannot simply be applied to California sea lions, probably due to the effects of the dive reflex induced during anesthesia.