Persons with conventionally treated insulin-dependent diabetes mellitus (IDDM) appear to be impaired in their ability to reduce fed state urea production appropriately in response to dietary protein restriction (Hoffer LJ, Taveroff A, and Schiffrin A. Am. J. Physiol. 272:E59-E67, 1997). To determine whether these conclusions apply to whole body sulfur amino acid (SAA) catabolism, we have used samples from this protocol to measure daily urinary sulfate excretion and fed state sulfate production after a high protein test meal prior to and following dietary protein restriction. Eight normal subjects and 6 IDDM subjects treated with twice-daily intermediate- and short-acting insulin consumed a mixed test meal containing 0.50 g protein/kg after adaptation to 4 days of a high protein intake (1.28 g protein/kg body weight) and again after 5 days of dietary protein restriction (0.044 g/kg). Adaptation to protein restriction decreased daily urinary sulfate and urea-N excretion by approximately 80%. Over the first 24 h of protein restriction urinary sulfate excretion decreased more than urea-N excretion for both the normal and IDDM subjects. Under conditions of a high prior protein intake, fed state sulfate production was normal for the IDDM subjects; protein restriction reduced fed state sulfate production by 51% (normal subjects) and 59% (IDDM subjects; NS). We conclude that whole body SAA metabolism is normal in CIT-IDDM prior to and following dietary protein restriction. SAA catabolism, as measured by fed state sulfate production, may be a convenient and useful measure to determine the extent of whole body protein dysregulation in IDDM.