Salinomycin, a new ionophore antibiotic, was tested and compared with lasalocid and monensin for preventing experimentally induced lactic acidosis. Five rumen-fistulated adult cattle were used in a 5 X 5 Latin square design, and the treatments were as follows: no treatment (control), 0.11 mg of salinomycin/kg of body weight (S1), 0.22 mg of salinomycin/kg (S2), 0.66 of lasalocid/kg, and 0.66 mg of monensin/kg. Acidosis was induced by intraruminal administration of a ground corn-corn starch mixture (50:50, 12.5 g/kg) once a day for up to 4 days. Antibiotics were administered along with grain-starch mixture. Rumen and blood samples were obtained before and at 6, 12, and 24 hours after each carbohydrate-antibiotic dosing to monitor acid-base status. Control and S1-treated cattle became ruminally acidotic within 54 hours, whereas cattle treated with S2, lasalocid, and monensin resisted acidosis for up to 78 hours after dosing. Cattle treated with S2, lasalocid, or monensin had higher rumen pH and lower L(+)- and D(-)-lactate concentrations than did control or S1-treated cattle. Rumen pH decrease to below 5.0 in S2-, lasalocid-, and monensin-treated cattle was not due to lactic acid, but to increased production of volatile fatty acids. Rumen propionate proportion increased initially in antibiotic-treated cattle, but after 48 hours, butyrate proportion increased significantly. Despite low rumen pH and high lactate concentration, lacticacidemia was not evident, and the systemic acid-base disturbance was mild in control cattle.(ABSTRACT TRUNCATED AT 250 WORDS)