The cytology of the interstitial cells of the testis of the river lamprey has been studied from the autumn when the upstream migration begins up to the completion of sexual maturation in the following spring. In the early stages of spermatogenesis the interstitial tissue consists of isolated interlobular connective tissue cells. During the winter these appear to increase in numbers and form compact groups sometimes showing an acinar type of structure. In the earlier stages of the secretory cycle the cytoplasm contains small osmiophilic and sudanophilic granules, which appear to aggregate to form much larger lipid positive masses. In the later stages of spermatogenesis in early spring, the interstitium accumulates large areas of lipid and cholesterol positive droplets and in fixed material the cytoplasm shows extensive vacuolization. In the terminal stages the cells undergo complete disintegration. It seems probable that the stage when the interstitium shows masses of lipid and cholesterol positive droplets represents a phase of degeneration and that the secretion of hormone occurs in earlier stages. No convincing evidence has been obtained for the presence of the enzyme steroid-3β-ol-dehydrogenase during the later stages of the secretory cycle. There is evidence that following the degeneration of the interstitium there may be a replacement of the secretory tissue by the transformation of residual connective tissue elements, which may then re-enter the secretory phase. The changes in the interstitium are paralleled by hypertrophy and evidence of lipid metabolism in the modified fibroblasts of the lobular wall and this tissue may also be involved in the secretory activity of the testis.