A method of continuous in vivo subcutaneous perfusion using Tyrode solution which permits direct analysis of pharmacological agents released in inflamed human skin is described. An examination was carried out using bioassay with three isolated organ preparations and spectrofluorometry. In dermographic skin of patients with urticaria pigmentosa the perfusate was consistently found to contain histamine. Additionally, smooth muscle-contracting activity against the rat uterus was detected but this was shown not to be due to bradykinin, histamine, serotonin, or acetylcholine. In urticaria factitia histamine was regularly recovered from the perfusate; bradykinin was detected in perfusates from only two of eight subjects studied. Similar experiments carried out in a group of control subjects revealed evidence of low concentrations of kinins in a minority of subjects but no other pharmacological activity was found.