Tissue distribution and residue depletion of oxytetracycline (OTC) following oral administration were evaluated in sea bream and sea bass under field conditions. Fish were held in floating cages placed in sea water and fed a commercial medicated diet containing 7.5 g/kg of OTC once daily for 14 days at a rate of 1.0% (75 mg a.i./kg) biomass per day. Muscle, liver, vertebrae, and skin with scales were sampled from fishes netted at different intervals during (2(nd), 4(th), 6(th), 10(th), and 14(th) day) and after treatment (10(th), 20(th), 30(th), 40(th), 50(th), and 60(th) day). OTC analyses were carried out by HPLC, after SPE extraction. In sea bream, a great variation in drug intake was evident from the inter-subject differences in OTC tissue concentrations. The highest recorded concentrations were in skin and pooled liver (7.70 +/- 6.71 mu g/g and 14.65 mu g/g at the 6(th) day, respectively). Vertebrae showed concentrations even six-fold higher than those in muscle, and reached steady state concentrations at the 40(th) day after the end of treatment (1.73 +/- 0.92 mu g/g), lasting until the end of the study. OTC concentrations in muscle were lower than in all the other tissues throughout the entire experiment and declined under 0.1 mu g/g 20 days after treatment ceased, In sea bass a high mortality not related to infectious diseases was observed and muscle samples had only traces or no detectable OTC levels even during medication.