The early reaction to the injection of silicone, collagen, and lyophilized heterologous fetal connective and cartilage tissues into the limiting zone deep dermis-superficial subcutaneous tissue was histologically examined in the pig and compared with clinical results. The inflammatory reaction to lyophilized heterologous fetal tissue is considerably more intense than that to collagen and silicone and lasts for several weeks. Therefore, it is not recommended for soft tissue filling in the face. Admitting an inferior antigenicity of fetal tissues, the authors suggest that enzymatically denaturalized collagen should be manufactured from heterologous fetal connective tissue, to be then further tested. The reaction of tissue to silicone and collagen is minimal. Silicone is preferred for dermal injections since in clinical experience it remains in the site of injection much longer. For subdermal injections, however, collagen is preferred. Based on experience with over 600 patients since 1958, the first author continues using liquid silicone. The lack of complications is probably a result of the fact that only small amounts (milliliters) of silicone were used in wrinkles or small depressions in the dermal layer and that from the beginning injection into the subcutaneous tissue was avoided. Since 1988 a new technique for the treatment of wrinkles and skin depressions with injections of dermal miniautografts has been used with satisfactory results.