The effect of i.v. administration of ionophores on metabolism in ruminants was investigated in two experiments. In Exp. 1, four Angus heifers were assigned randomly to receive i.v. monensin (18 mg, n = 2) or vehicle (control, n = 2). Samples were collected from indwelling vena cava cannulas from -60 to 240 min. Concentrations of K, Mg (P less than .05) and P (P less than .10) were lower and glucose (GLU) and free fatty acids (FFA) were higher (P less than .05) in monensin-treated than in control heifers. Serum insulin (INS) initially declined and subsequently increased (P less than .05) following monensin administration. A second experiment was conducted to determine the effect of a higher dose of monensin and the effect of lasalocid on minerals and metabolites. Angus (n = 3) and Hereford (n = 3) steers were randomly assigned to treatments in two 3 x 3 latin square designs. Treatments were i.v. administration of monensin, lasalocid or vehicle (ethanol) administered on three consecutive days. Administration of monensin, but not vehicle or lasalocid, resulted in ataxia, hypernea, polyuria and anorexia for approximately 2 h. Plasma concentrations of K, P and Mg were suppressed (P less than .05) by monensin, but not by vehicle or lasalocid administration. The decrease in K was preceded by a transient increase in K 15 min after administering monensin. Concentrations of GLU and FFA increased (P less than .05) following monensin administration. Concentrations of INS were lower from 60 to 120 min and greater at 180 and 240 min compared with -60 to 0 min from monensin administration (P less than .05). These results provide first evidence of an effect of monensin on metabolism in ruminants independent of alterations in ruminal microbial metabolism.