The effects of pregnancy and type 1 diabetes [insulin-dependent diabetes mellitus (IDDM)] on protein metabolism are still uncertain. Therefore, six normal and five IDDM women were studied during and after pregnancy, using [¹³C]leucine and [²H₅]phenylalanine with a hyperinsulinemic-euglycemic clamp and amino acid infusion. Fasting total plasma amino acids were lower in pregnancy in normal but not IDDM women (2,631 ± 427 vs. 2,057 ± 471 and 2,523 ± 430 vs. 2,500 ± 440 µmol/l, respectively). Whole body protein breakdown (leucine) increased in pregnancy [change in normal (N) and IDDM women (D) 0.59 ± 0.40 and 0.48 ± 0.26 g · kg¹ · day¹, both P < 0.001], whereas reductions in protein breakdown due to insulin/amino acids (N 0.57 ± 0.19, D 0.58 ± 0.20 g · kg¹ · day¹, both P < 0.001) were unaffected by pregnancy. Protein breakdown in IDDM women was not higher than normal, and neither pregnancy nor type 1 diabetes altered the insulin sensitivity of amino acid turnover. Nonoxidized leucine disposal (protein synthesis) increased in pregnancy (N 0.67 ± 0.45, D 0.64 ± 0.34 g · kg¹ · day¹, both P < 0.001). Pregnancy reduced the response of phenylalanine hydroxylation to insulin/amino acids in both groups (N 1.14 ± 0.74, D 1.12 ± 0.77 g · kg¹ · day¹, both P < 0.05). These alterations may enable amino acid conservation for protein synthesis and accretion in late pregnancy. Well-controlled type 1 diabetes caused no abnormalities in the regulation of basal or stimulated protein metabolism.