We have investigated the development of the Harderian glands of female Syrian hamsters from birth to 8 months of age. The effects of melatonin injections on Harderian gland histology and porphyrin deposits of female hamsters exposed to two different temperatures were also studied. The morphology of the Harderian glands from 30-day-old female hamsters resembled those of sexually mature adult animals. The intraluminal area occupied by porphyrins increased significantly between 20 to 30 days of age. However, the relative number of mast cells per mm2 rose between 30 to 90 days. Both porphyrins and mast cell numbers appeared clearly reduced in the 8-month-old group. Secretory cells characterized by large lipid droplets (type II cells) were not observed. Daily afternoon injections of 25 micrograms of melatonin to female hamsters exposed to 22 degrees C for 14 weeks resulted in the discontinuity of estrous cyclicity, a marked decrease in the intraluminal area occupied by porphyrins, a reduction of the number of mast cells per mm2, and in a marked augmentation of the number of type II cells per mm2. Although the administration of similar dosages of melatonin to hamsters exposed to an environmental temperature of 32 degrees C did not interrupt estrous cycles, a clear reduction of the area occupied by porphyrins was observed. However, the number of mast cells and type II cells per mm2 was unaffected in these animals. Our results suggest that hormones other than ovarian steroids are involved in the regulation of the female hamster Harderian glands. The possible role of melatonin on Harderian gland metabolism is discussed.