This study evaluated the effect of 2'-deoxy-5-fluorouridine (FUDR) on the regeneration of the liver following partial (68%) hepatectomy in the rat. Male Sprague-Dawley rats weighing between 190 and 240 g underwent partial hepatectomy under ether anesthesia. Twelve hours postoperatively rats received intraperitoneal injections of 2'-deoxy-5-fluorouridine or 0.9% NaCl solution as follows: Group I, 0.9% NaCl solution (n = 49); Group II, 89 mg 2'-deoxy-5-fluorouridine/kg of body weight (n = 25); and Group III, 178 mg 2'-deoxy-5-fluorouridine/kg of body weight (n = 24). Sham groups underwent celiotomy and liver palpation followed by 0.9% NaCl solution injections (n = 5) or low dose 2'-deoxy-5-fluorouridine (n = 5) and high dose 2'-deoxy-5-fluorouridine (n = 5). The regenerative ability of the liver was evaluated by weight and deoxyribonucleic acid synthesis in the liver remnant. RESULTS Both low and high dose 2'-deoxy-5-fluorouridine delayed the peak of deoxyribonucleic acid synthesis from 36 to 72 hr as compared to control animals which had maximal synthesis at 25 to 36 hr postoperatively (P less than 0.01). Weight of the liver remnants demonstrated a similar pattern. CONCLUSIONS High doses of 2'-deoxy-5-fluorouridine administered intraperitoneally delay, but do not inhibit, liver regeneration following partial (68%) hepatectomy as reflected by DNA synthesis and weight of the remnant.