The MCR of PRL was measured in male, female, pregnant, and lactating mice of a high (C3H/St) and a low (C57BL/St) mammary tumor strain. Mouse PRL was administered by a single injection in the jugular vein of unanesthetized mice pretreated with 2-Br-α-ergocryptine, and sera were collected from the orbit at frequent intervals. Sera were assayed for PRL with a homologous RIA. The MCR of PRL in male mice (C3H/St, 0.45 ± 0.02; C57BL/St, 0.36 ± 0.02 ml/min) was 2–3 times higher than that in virgin females (C3H/St, 0.21 ± 0.01; C57BL/St, 0.10 ± 0.01 ml/min). The MCR did not change significantly during advanced pregnancy (C3H/St, 0.22 ± 0.02; C57BL/St, 0.06 ± 0.01 ml/min). However, the MCR increased sharply in lactating mice (C3H/ St, 0.42 ± 0.02; C57BL/St, 0.50 ± 0.04 ml/min). Except during nursing, the MCR was substantially higher in the high tumor C3H/St strain than in the low tumor C57BL/St strain. The secretion rate of PRL was highest in lactating mice (C3H/St, 123 ± 6; C57BL/St, 206 ± 29 ng/min) and lowest in virgin females (C3H/St, 7.5 ± 1.3; C57BL/St, 7.3 ± 1.6 ng/min). The secretion rate in male mice (C3H/St, 13.4 ± 2.0; C57BL/St, 10.8 ± 2.7 ng/min) was statistically indistinguishable from that in virgin females. Both strains had similar secretion rates at all stages, except during lactation when the secretion rate was higher in the C57BL/St strain. The results suggest that 1) the serum concentrations of PRL in mice do not always accurately reflect its level of secretion, 2) the rapid clearance rate of PRL may be associated with the development of mammary tumors in some strains of mice, and 3) PRL may have a wider function in male mice than is recognized. © 1979 by The Endocrine Society.