To determine the effect of repeated ketoprofen (K) administration to surgically castrated bulls on cortisol, acute-phase proteins, immune function, feed intake, growth and behavior, 50 Holstein x Friesian bulls (11 mo old; 300 +/- 3.3 kg) were assigned to one of five treatments: 1) untreated control (C); 2) surgical castration at 0 min (S); 3) S following an i.v. injection of 3 mg/kg of BW of K at -20 min (SK1); 4) S following 1.5 mg/kg of BW of K at -20 and 0 min (SK2); or 5) S following 1.5 mg/kg of BW of K at -20 and 0 min and 3 mg/kg of BW of K at 24 h (SK3). Castration acutely increased plasma cortisol concentrations in S- and K-treated animals compared with C, with no differences in peak and interval to peak cortisol responses among the castration groups. Overall, the integrated cortisol response was greater (P < 0.05) in the castrates than in C, whereas K treatments decreased (P < 0.05) this response compared with S alone, with no differences between K treatments. Plasma haptoglobin and fibrinogen concentrations were increased (P < 0.05) on d 3 in the castration groups compared with C as the result of tissue trauma induced by castration, whereas SK1 and SK2 had lower (P < 0.05) haptoglobin concentrations than S animals. On d 1, concanavalin A-induced interferon-gamma production was suppressed (P < 0.05) in S and SK3 compared with C, SK1, and SK2 animals. Overall from d 1 to 33, DMI were lower (P < 0.05) in S, SK1, and SK3 than in C animals. From d -1 to 35, ADG were lower (P < 0.05) in S, SK2, and SK3 compared with C animals. A higher (P < 0.05) incidence of standing postures and lower incidence of lying postures was observed in S compared with C during the first 6 h after treatment. However, the higher (P = 0.02) incidence of abnormal standing activities observed for S was reversed (P < 0.05) by the K treatments. In conclusion, surgical castration increased plasma cortisol and acute-phase proteins and decreased immune function, feed intake, and growth rate. Ketoprofen effectively reduced the cortisol response to castration, but there was no advantage in treating with two split doses of K (1.5 mg/kg of BW per dose). A repeated K dose 24 h after treatment (3 mg/kg of BW) had no influence on changes in acute-phase proteins and immune response. Systemic analgesia with K is an effective method for alleviating acute inflammatory stress associated with castration.