The pharmacokinetics of doxycycline were investigated in sheep after oral (PO) and intravenous (IV) administration. The IV data were best described using a 2- (n = 5) or 3- (n = 6) compartmental open model. Mean pharmacokinetic parameters obtained using a 2-compartmental model included a volume of distribution at steady-state (V(ss)) of 1.759+/-0.3149L/kg, a total clearance (Cl) of 3.045+/-0.5264mL/kg/min and an elimination half-life (t(1/2beta)) of 7.027+/-1.128h. Comparative values obtained from the 3-compartmental mean values were: V(ss) of 1.801+/-0.3429L/kg, a Cl of 2.634+/-0.6376mL/kg/min and a t(1/2beta) of 12.11+/-2.060h. Mean residence time (MRT(0-infinity)) was 11.18+/-3.152h. After PO administration, the data were best described by a 2-compartment open model. The pharmacokinetic parameter mean values were: maximum plasma concentration (C(max)), 2.130+/-0.950microg/mL; time to reach C(max) (t(max)), 3.595+/-3.348h, and absorption half-life (t(1)/(2k)(01)), 36.28+/-14.57h. Non-compartmental parameter values were: C(max), 2.182+/-0.9117microg/mL; t(max), 3.432+/-3.307h; F, 35.77+/-10.20%, and mean absorption time (MAT(0-infinity)), 25.55+/-15.27h. These results suggest that PO administration of doxycycline could be useful as an antimicrobial drug in sheep.