Although our previous studies demonstrated marked changes in the activities of hydrolytic enzymes in guinea pigs afflicted with experimental allergic encephalomyelitis (EAE), it is possible that at least some parts of them were due to the effects of Freund's complete adjuvant (FCA) per se used for immunization. Thus we tried to find the property of the enzymatic changes in the tissues of limb muscle, heart muscle, spleen, liver, kidney, brain, spinal cord and serum induced by the administration of FCA alone to the guinea pigs. FCA caused rather intensive enzymatic changes in evey organ tested. When the patterns of these enzymatic changes were compared with those of the animals afflicted with EAE, a significant correlation was seen only in forelimb muscle at 1 week after the injection of the agents, whereas at 2 weeks significant correlations were seen in heart and liver. Although these results indicate that in some organs there are some similarities between the two experimental conditions, the degree of determination for this phenomenon was not high, being 28% at the highest. This means that most of the enzymatic changes seen in the animals afflicted with EAE could not be explained by the effects of FCA. It was concluded that FCA causes unique and systemic enzymatic changes when administered to the animals.