Erythrocyte levels of polyamines, especially of spermidine are greatly elevated during the course of liver regeneration. In contrast to putrescine and spermine levels, from the tenth hour to the fourth week after partial hepatectomy, correlation has been observed between the elevation of liver and erythrocyte spermidine concentrations. Substituting drinking water with 2% alpha difluoromethylornithine (alpha-DFMO) commencing 48 hr prior to partial hepatectomy and continuing until death, though ineffective in inhibition of liver [3H]-thymidine incorporation, prevented the rise in hepatic putrescine concentrations (without modifying those of spermidine and spermine) and correlatively decreased red blood cell (RBC) spermidine levels. Thus, an excess of liver spermidine produced from an excess of newly synthetized putrescine could be released in blood and taken up by erythrocytes, especially as affinity of RBC for spermidine is at least 30 fold higher than that for putrescine. In vivo the spermidine half-life in RBC was estimated to be 2.5-3.0 hr, which could explain the elevation of erythrocyte and liver spermidine levels. The elevation of erythrocyte spermidine concentration is not correlated to that of the regenerating liver weight but dependent on the extent of partial hepatectomy. The elevation of erythrocyte spermidine concentrations, which appeared to be linked to the cellular proliferating activity, could contribute to determine intratumoral proliferation in cancerous patients.