Human urine samples, purified on octadecasilyl-silica cartridges, contained immunoreactive angiotensin I, II, arginine vasopressin and oxytocin. The daily excretion of these peptides in healthy volunteers was 190.00±38.43 (n=12), 17.48±3.09 (n=12), 63.43±14.84 (n=8) and 13.52±1.42 (n=7) pmol/24 hr, respectively (mean±s.e.m.). Patients with a history of anaphylactoid reactions to drugs or food additives showed clinical symptoms such as urticaria, flush, nausea, dizziness and hypotension after oral provocation with cyanocobalamine, propyphenazone, acetylsalicylic acid and sodium benzoate. In five of the seven patients, angiotensin I and II were increased several fold in the urine fractions after symptoms were reported. The average increase in the urine concentration of both peptides was fourfold and 5.5-fold. In three out of five patients, the mean excretion of arginine vasopressin and oxytocin immunoreactive material was also elevated by a factor of 5.7 and 4.4, respectively. Oral provocation with a placebo failed to elicit anaphylactoid symptoms or an increase in the urine levels of angiotensin I or angiotensin II. Angiotensin I and angiotensin II-like immunoreactivity could be characterized on HPLC as Ile5-angiotensin I, Ile5-angiotensin II and angiotensin II metabolites. HPLC characterization of immunoreactive arginine vasopressin and oxytocin in two different gradient systems showed retention times different than the retention times of the corresponding synthetic standard peptides indicating that both peptides are not authentic AVP and OXT. These results suggest that angiotensin I and angiotensin II may be involved in the clinical events observed during some forms of anaphylactoid reactions.