Experimental study on histamine liberation in a postanaphylactic phase of allergy was carried out employing an air pouch model of allergic inflammation in rats. The antigen used was azobenzenearsonate-con-jugated acetyl bovine serum albumin. Synthesis and liberation of histamine took place in the inflammatory pouch in the dorsum of the allergic rats, and brought about a gradual rise in the histamine level in the pouch fluid with a peak at 24 h after the antigen challenge. The time course of the histamine level in the pouch fluid was quite similar to that of histidine decarboxylase activities in the inflammatory tissues. et-Fluoromethylhisti-dine reduced the histamine level in the postanaphylactic phase, although it had been ineffective in the anaphylactic phase. A substance capable of increasing histamine production by bone marrow cells was found in the pouch fluid of allergic rats, while it was absent in the normal rat serum and pouch fluid of nonsensitized rats. The histamine-production-increasing activity rose until 24 h after the antigen challenge, but fell at 48 h in parallel with changes both of histamine levels in the pouch fluid and histidine decarboxylase activity in inflammatory tissues. The histamine-production-increasing factor is thought to be a protein, since it was inactivated by treatment with heal (70°C for 30 min) or trypsin. Its molecular weight was estimated to be between 25,000 and 40,000.