The amphibian Xenopus laevis adapts the colour of its skin to the colour of its background, by the release of the pro-opiomelanocortin-derived peptide alpha-melanophore-stimulating hormone from the pars intermedia of the pituitary gland. Suprachiasmatic neurons play an important role in adaptation to a light background as they produce the neurotransmitters GABA, dopamine and neuropeptide Y, which inhibit the release of alpha-melanophore-stimulating hormone. These factors are transported to axon varicosities contacting the melanotrope cells. In these varicosities GABA resides in electron-lucent vesicles and neuropeptide Y and dopamine coexist in electron-dense vesicles. In this study the effects of background adaptation on the morphology of the varicosities in the pars intermedia were studied, using immunoelectron microscopy and morphometry with freeze-substitution-fixed material. Varicosities were found singly and in clusters throughout the pars intermedia. Varicosities were identified by the presence of electron-dense and electron-lucent secretory vesicles, the latter being immunopositive for anti-GABA. Both varicosity types revealed active zones with exclusively GABA-containing vesicles in contact with the presynaptic membrane. When white- and black-adapted animals were compared, significant background effects were found with respect to the organization of the varicosities: the density of varicosity profiles was twice as high in white-adapted animals as in black-adapted ones, due to an increase in density of the clustered varicosities. Furthermore, in white-adapted animals varicosities were about twice as large as in black-adapted animals. With respect to vesicle types, single and clustered varicosities showed a differential effect. For both the population of electron-lucent and electron-dense vesicles, single varicosities showed equal numbers in white- and black-adapted animals, but clustered varicosities showed higher numbers of electron-lucent and electron-dense vesicles in black-adapted animals, indicating storage of neurotransmitters. Finally, in varicosities of white-adapted animals the number and size of the active zones and the number of electron-lucent vesicles attached to the active zones, were about twice as high as in black-adapted animals, indicating a stronger GABA release. It is concluded that the profound effects of environmental light conditions on synaptic structure and substructure in the Xenopus pars intermedia are related to a changed release activity of neurotransmitters inhibiting the activity of the melanotrope cells.