A patient with pyoderma gangrenosum without associated disease was studied. Routine investigations showed several abnormalities. High ESR, high alkaline phosphatase and glutamyl transferase (gamma-GT) levels, low iron and iron binding capacity, altered protein spectrum, presence of Staphylococcus aureus and group G hemolytic streptococci in ulcer culture, higher than normal antistreptolysin titers in the serum, and perivascular infiltration in the skin. Biochemical investigations aimed at finding any excessive hydrolytic activity did not reveal the presence of neutral proteases in circulation leaked out from PMN-leukocytes or elsewhere. Lysozyme levels were higher than normal, amylase and lipase levels were normal and 5' nucleotidase levels were below normal range. TCA-soluble polypeptides were present in the serum at levels two times higher than those in normal individuals. Immunochemical investigations showed the absence of immune complexes in the serum but presence of high amounts of C-reactive protein. Total complement activity was higher than normal and so was C3c level. Clq, C4, and C3d levels were within normal range. Biologic studies showed the presence of a factor in patient serum that made guinea pig skin hard, painful, erythematous, and eventually hairless, but not necrotic. A similar factor was either absent in normal serum or present in very low concentration. After salazopyrine treatment, all the above mentioned abnormalities corrected except that 5' nucleotidase activity remained slightly lower than normal, alkaline phosphatase levels remained slightly higher than normal, and C-reactive protein levels remained very high, though lower than those during intense disease activity.