The epidermis and corium of rat right hind paw were investigated both histologically and histometrically after a subplantar injection of aerosil, formalin, carrageenin or Freund's complete adjuvant. The thickness of the epidermis and corium was determined on 5 rats respectively at 12 different times between 0.5 and 480 h post-treatment. Paw swelling was measured plethysmometrically on living rats. The left paw of untreated rats as well as the saline-injected and the untreated left paw of carrageenin-treated and adjuvant-treated animals respectively served as controls. Results 1. After the injection of the 4 substances, an acute inflammation developed maximally 4 to 24 h post-treatment in the corium. The thickness of the corium increased simultaneously with paw swelling. 2. Epidermal hyperplasia set in after a lag-phase of 12 h following the injection of formalin, carrageenin and adjuvant. 3. After injection of aerosil a subcutaneous oedema developed but no epidermal hyperplasia occured. 4. The formation of granulation tissue and necroses in the corium was seen only in the adjuvant-treated group 4 to 20 days post-treatment. At the same time, epidermal hyperplasia reached an absolute maximum. 5. The disturbance of nutrition and the lack of oxygen in the inflamed corium is possibly responsible for the initiation and persistence of the hyperplasia.