For verifying catabolic states in insulin-dependent patients and dogs the method estimating urea production rates with13C and with doubly15N labeled urea, respectively, has been established. For a fast steady state of urea tracer dilution, a prime of 600 times the continuous infusion rate had to be injected. Urea was isolated from plasma samples by protein precipitation and cation exchange chromatography with a consecutive derivatization of the dried urea fraction (trimethylsilyl derivatives). The masses of the fragment ions m/z 189 (14N14N), 190 (14N15N) and 191 (15N15N) urea are monitored to estimate the [15N2]urea frequency in the overall body urea pool in mol percent excess (MPE). 1 to 15 ng of derivatized urea were measured efficiently. An excellent correlation between expected standard and measured MPE (r= 0.9977) was achieved from solutions containing 1 to 7% [15N2]urea. The interassay coefficient of variation amounted to < 10% for a [15N2]urea portion of ≥ 3%.