A radioimmunoassay for plasma 3-methylhistidine (3MeHis) measurements has been developed. The assay has no significant crossreactivity with 18 other amino acids including histidine, carnosine, anserine, and creatinine. In normal subjects who have eaten no meat for 36 hours, plasma levels are constant over a 24-hour period (8.78 ± 0.48 μmol/L, mean ± SD). The use of 3MeHis for the assessment of intestinal protein absorption and its potential use as a marker of protein degradation were evaluated by studying its plasma kinetics. The absorption of the free 3MeHis is rapid and reaches a peak after 75 minutes. The peak is delayed after meat ingestion and reaches a maximum after 180 minutes. The ratio of the 75- to 180-minute 3MeHis levels was 1.40 ± 0.06 for pure 3MeHis and 0.78 ± 0.06 after meat ingestion ( P < 0,001). Peak height and area under the plasma concentration versus time curve were proportional to the dose received, indicating first order kinetics for 3 MeHis. It has a half-life of 12.2 hours, a metabolic clearance rate of 0.08 L/h and volume of distribution is 11.7 ± 1.7 L as calculated from the serum values which were obtained up to 24 hours after oral 3MeHis administration. Its endogenous production can therefore be calculated to be 116 μmols per day in young subjects. Thus, the radioimmunoassay develops the potential of this amino acid as a marker of protein degradation and absorption for physiological investigations.