Using a histochemical method for the visualization of cholinesterase activity in neurons, we have observed developmentally transient expression of acetylcholinesterase (AChE) in cortical pyramidal neurons of the rat brain. Depending on the extent of the deposition of AChE reaction product, several types of cortical neurons could be visualized. We designated neurons with moderate-to-high staining intensity as AChEH and neurons with relatively lower staining intensity as AChEL. At birth (P0), very little AChE activity was found within cortical neurons. Between P1-P4, there was a gradual emergence of AChE-stained cortical neurons. At this stage, the majority of these neurons were of the AChEL type. At P5-P7 we observed an abrupt increase in AChE-stained cortical neurons. The number and the staining intensity of these neurons was at a peak at P8-P10. At this age range, the majority of these neurons were of the AChEH variety and displayed morphological characteristics of cortical pyramidal neurons. At P11-P15, there was an abrupt decrease in the number of AChEH neurons. After P15, the density and staining intensity of cortical AChE-positive (cholinergic) axons gradually increased. Nevertheless, AChEL pyramidal neurons were detected through these fibers up to P21. At P21, a dense plexus of AChE-positive axons was observed in all cortical areas while very little AChE reaction product was visible in pyramidal neurons, and this pattern continued into adult life. When the adult cortex was denervated from its AChE-positive axons by lesions of the nucleus basalis magnocellularis, many AChEL pyramidal neurons were uncovered.(ABSTRACT TRUNCATED AT 250 WORDS)