The present study was undertaken to elucidate the effect of calcium ion on the granulation tissue formation during wound healing. Male guinea pigs of Pilbright strain were chosen as the experimental animal. An appropriate open wound was aseptically made on the dorsum of the guinea pigs, which was then equipped with a sterile Teflon-cylinder. The amounts of granulation tissues developed within the cylinder were determined during 10 day period of the observation. In addition, various concentrations of CaCl2 were applied on the wound surface for up to 3 days after the wounding. Calmodulin contents in the granulation tissue were also determined using calmodulin-deficient phosphodiesterase prepared from bovine heart. Purified pig skin epidermal calmodulin was used as the standard. The results obtained were as follows: The amount of the granulation tissue increased in a stepwise manner during 3, 5, 7, and 10 days after the wounding. Calmodulin content in the granulation tissue was maximal on the day 3 after the wounding, waned on the day 5, and remained low on the days 7 and 10. A significant augmentation of the granulation tissue production as well as of calmodulin content was observed when CaCl2 was applied on the wound surface during 3 days after the wounding. These results suggest that calcium ion might have a significant role on granulation tissue development, possibly through the Ca++-calmodulin system, during early stages of wound healing process.