Forty wether lambs were used in a 2 x 4 factorial arrangement to determine the response of animal performance, muscle growth, proteinase activity, and meat tenderness to beta-adrenergic agonist (BAA) supplementation. Lambs were fed a finishing diet with or without 4 ppm of L644,969 and slaughtered after 0, 2, 4, and 6 wk of treatment. The ADG was higher (P < .05) in the treated than in the control lambs after 2 wk and returned to control levels thereafter. Semitendinosus weight and calpastatin activity were higher and mu-calpain activity was lower in the treated than in the control lambs after 2, 4, and 6 wk. Cathepsin B activity was higher (P < .01) and cystatin-like activity was lower (P < .05) after 2 wk in treated than in control lambs but returned to control levels thereafter. Longissimus protein:DNA was higher after 4 (P < .05) and 6 (P < .01) wk in the treated lambs than in the controls. The concentration of RNA and RNA:DNA ratio were higher (P < .01) in the longissimus and semitendinosus muscles in the treated lambs after 2 wk and remained higher throughout the study. Semitendinosus protein and RNA content were higher after 2, 4, and 6 wk and DNA content was higher after 2 and 6 wk in the treated than in the control lambs. Longissimus shear-force values were higher (P < .001) in the treated than in the control lambs at all slaughter end points. These data indicate a rapid alteration of muscle growth, activity of the calpain-calpastatin system, and meat tenderness during BAA treatment.(ABSTRACT TRUNCATED AT 250 WORDS)