To study the effects of intravenous doxycycline hyclate on protein malnourished rats, 20 male Sprague-Dawley rats, weighing 234 to 277 g, were protein depleted for 6 weeks then randomly assigned to one of two groups: group I (10 rats), total parenteral nutrition with intravenous doxycycline hyclate injections, group II (10 rats), total parenteral nutrition with normal saline injections. Both groups were then protein repleted for 7 days. Body weight; fluid intake; urine output; liver, spleen, and lung weights; nitrogen content; and serum proteins were measured. The antibiotic dosage given was 10 mg/kg body weight/day or 0.1688 +/- 0.0046 mg/kg. There was no significant difference in starting weight, weight after 6 weeks of protein depletion, weight at sacrifice, or weight gain between groups I and II. Average fluid intake/day for groups I (50 +/- 2 ml) and II (51 +/- 3 ml) were not statistically significant. There was no significant difference in average urine output/day nitrogen balance, liver weight, and liver nitrogen, spleen and lung weights, or serum albumin levels (Groups I, 2.84 +/- 0.48 g%, Group II, 2.72 +/- 0.24 g+). Intravenous doxycycline hyclate does not appear to have a protein catabolic effect on protein malnourished rats receiving total parenteral nutrition.