One feedlot trial (116 d; 192 steers) with a factorial arrangement of treatments was conducted to determine effects of supplemental fat and ionophores in corn-based finishing diets. Factors were level of fat (0 or 4% tallow) and ionophore type (none [N], lasalocid [L], monensin plus tylosin [MT], or daily rotation of L and MT [LMT]); L, M, and T were fed at 31, 25, and 10 ppm (DM basis), respectively. Fat and ionophore interacted for DMI (P < .10), ADG (P < .01), and gain:feed G/F, P < .05). Compared with 0%-fat diets, 4% fat decreased (P < .005) DMI by steers fed MT by 8.9%. In 0%-fat diets, MT increased (P < .05) ADG and G/F compared with N or L; however, this increase was negated or reversed in 4%-fat diets. Fat and ionophore interacted (P < .16) on dietary NE concentration. In the 0%-tallow diet, MT increased NEm and NE(g) by 5.1 and 7.0%, respectively, but MT had not effect on NE concentration of the 4%-tallow diet. Alternate feeding of L and MT did not increase animal performance above that of separate, continuous feeding. Six ruminally fistulated steers were used in a metabolism study to evaluate potential mechanisms underlying the interactions observed in the feedlot trial. Treatments were the same as the feedlot trial, except that LMT was not included. Ruminal digesta kinetics were not altered (P > .30) by the addition of fat or ionophores to the diet. Fat and ionophore interacted (P < .05) for molar proportions of ruminal acetate and propionate.(ABSTRACT TRUNCATED AT 250 WORDS)