In all mammalian species studied the haematocrit (hct) declines after birth in the absence of any known nutritional deficiencies. The glycoprotein hormone, erythropoietin (Epo), is essential for normal red blood cell production. The aims of this study were 1) to investigate the changes in plasma Epo during the normal post-natal decrease in hct in lambs; 2) to compare the effects of chronic and acute haemorrhage in neonatal lambs; and 3) to test the hypothesis that the Epo response to haemorrhage is blunted in the neonatal period. Twenty-one lambs (0-9 weeks of age) were studied; group I (n = 8) were used to document normal post-natal changes (98 samples); group II (n = 7) lambs were haemorrhaged repetitively during weeks 3-6 (95 samples); group III (n = 6) lambs were bled once in the first 3-week period. In the group I (control lambs) the hct decreased from 30.6 +/- 1.3 (weeks 1 & 2) to a nadir of 23.2 +/- 0.8 (75.8% of initial value) in the 6th week, and the plasma Epo declined from 25.7 +/- 4.9 (week 1) to 12.3 +/- 1.0 mU/ml (week 6). In group II, the lambs were bled repetitively, a total of 510 +/- 32 ml blood being removed during weeks 3-6, the hct was 18.7 +/- 0.8 (81% of hct at nadir in controls) in week 6, and Epo was 26.9 +/- 13.3 in week 3, 23.4 +/- 3.6 mU/ml in week 6.(ABSTRACT TRUNCATED AT 250 WORDS)