The term neurosteroid applies to those steroids that are synthesized in the nervous system, from cholesterol or other blood-borne steroidal precursors, and that accumulate in the nervous system to levels that are at least in part independent from steroidogenic gland secretion. Both glial cells and neurons participate in neurosteroid biosynthesis and metabolism. Several neurosteroids are involved in auto/paracrine mechanisms involving regulation of target gene expression and/or effects on membrane receptors (particularly those for neurotransmitters). An additional unexpected mechanism of steroid action is reported here: pregnenolone binds to neural microtubule-associated protein of type 2 (MAP2) and increases both the rate and extent of tubulin polymerization, forming microtubules of normal electron microscopic appearance. This novel mechanism may play a role in regulating microtubule formation and dynamics and thus neuronal plasticity and function.