To determine the effects of fetal beta-2 agonist exposure on fetal hepatic glycogen metabolism, we infused ritodrine at a rate of 1.3 +/- 0.4 microgram/kg/min (mean +/- SD) for 24 h into six chronically catheterized twin fetal lambs starting between 128 and 134 days gestation. The control twins received 0.9% saline at 1.2 +/- 0.12 ml/kg/h. In addition, 15 uncatheterized fetuses were killed between 115 and 148 days gestation as unoperated controls. Ritodrine infusion produced a 1.7-fold elevation in fetal serum glucose level, from 23 +/- 5 to 42 +/- 15 mg/dl, and a 2-fold elevation in serum insulin level, from 16 +/- 5 to 34 +/- 8 mg/ml, p less than 0.01. Hepatic glycogen content increased 7-fold in the uncatheterized controls between 115 and 148 days gestation (r = 0.9, p less than 0.001). Ritodrine infusion reduced hepatic glycogen content by 50% from 179 +/- 19 micrograms/mg in twin controls to 90 +/- 25 micrograms/mg in the ritodrine-infused twins, p less than 0.001. Hepatic glycogen phosphorylase kinase activity was elevated 1.3-fold from 0.149 +/- 0.100 mU/mg protein in control twins to 0.186 +/- 0.007 mU/mg protein in the ritodrine infused twins, p less than 0.001. Glycogen phosphorylase a activity was also increased 1.4-fold from 8.60 +/- 0.76 nM NADPH/min/mg protein in control twins to 11.85 +/- 0.68 nM NADPH/min/mg protein in the ritodrine infused twins, p less than 0.001.(ABSTRACT TRUNCATED AT 250 WORDS)