At the start of this review, factors were deemed trophic if they stimulated mitosis, permitted neural cell survival, promoted neurite sprouting and growth cone motility, or turned on a specific neuronal phenotype. The in vitro evidence from cell cultures is overwhelming that both neurotransmitters and neuropeptides can have such actions. Furthermore, the same chemical can exert several of these effects, either on the same or on different cell populations. Perhaps the most striking example is that of VIP, which can stimulate not only mitosis, but also survival and neurite sprouting of sympathetic ganglion neuroblasts (Pincus et al., 1990a,b). The in vivo data to support the in vitro experiments are starting to appear. A role for VIP in neurodevelopment is supported by in vivo studies that show behavioral deficits produced in neonatal rats by treatment with a VIP antagonist (Hill et al., 1991). The work of Shatz' laboratory (Chun et al., 1987; Ghosh et al., 1990) suggests that neuropeptide-containing neurons, transiently present, serve as guideposts for thalamocortical axons coming in to innervate specific cortical areas. Along similar lines, Wolff et al. (1979) demonstrated gamma-aminobutyric acid-accumulating glia in embryonic cortex that appeared to form axoglial synapses and suggested the possibility that gamma-aminobutyric acid released from the glia might play a role in synaptogenesis by increasing the number of postsynaptic thickenings. Meshul et al. (1987) have provided evidence that astrocytes can regulate synaptic density in the developing cerebellum. The work of Zagon and McLaughlin (1986a,b, 1987) has shown that naltrexone, an antagonist of the endogenous opioid peptides, affects both cell number and neuronal sprouting. Lauder's laboratory (Lauder et al., 1982) has shown a role for 5-HT in regulation of the proliferation of numerous cell types. These studies illustrate another important point, that neurotransmitters and neuropeptides function in communication not only between neurons, but also between neurons and glial cells, and between glial cells. Given that astrocytes can express virtually all of the neural receptors and can produce at least some of the neurotransmitters and neuropeptides, they must now be considered equal partners in the processes of intercellular communication in the nervous system, including the trophic responses. The actions of neurotransmitters and neuropeptides have to be considered in terms of a broad spectrum of actions that range from the trophic actions described in this review, to the classic transmitter actions, to potential roles in neurotoxicity.(ABSTRACT TRUNCATED AT 400 WORDS)