Apoptosis, the major form of programmed cell death (PCD), is executed through a proteolytic cascade that can be differentially engaged by various extracellular signals. Modulation of both the sensitivity to PCD and of the actual sequence of apoptotic events is, therefore, strongly dependent on cell interactions. This paper reviews the use of a retinal explant preparation as a model of the organized nervous tissue, to study the effects of neural messengers in the control of sensitivity to apoptosis. Studies of retinal explants showed that dopamine, glutamate and nitric oxide may have anti-apoptotic effects upon developing retinal cells. At least the effects of nitric oxide are clearly paracrine. In addition, preliminary evidence has been gathered of a role for gap junctional communication in the control of sensitivity of retinal cells to the induction of apoptosis. These findings underscore the importance of selective cell interactions in the control of PCD in the developing nervous system.