Sixteen clones, recently isolated from the PC12 nerve cell line, were analysed for a variety of markers and activities. Two endoplasmic reticulum (ER) luminal markers, the chaperone protein BiP and the major Ca2+ storage protein calreticulin, as well as the 40-kD rough ER membrane marker and the plus-end-directed mirotubule motor protein, kinesin, were found to be expressed at similar levels. These results suggest that the size of the ER, the function of microtubules and the capacity of the rapidly exchanging Ca2+ store do not change substantially among the clones. Other proteins expressed at comparable levels were synapsin I and IIa, members of a nerve cell-specific protein family known to bind synaptic vesicles to the cytoskeleton. In contrast, another ER membrane protein, calnexin, and the markers of secretory organelles were found to vary markedly. One clone (clone 27) completely lacked both chromogranin B and secretogranin II, the proteins contained within dense granules, and synaptophysin, a marker of clear vesicles. Other clones expressed these markers to variable and apparently mutually unrelated levels. Marked variability was observed also in the uptake of exogenous catecholamines, in their release both at rest and after stimulation, and in nerve growth factor-induced differentiation. These results provide indirect information about the mechanisms that regulate the expression of structures and activities in PC12 cells. Of particular interest is clone 27, which appears globally incompetent for regulated secretion and might therefore be a valuable tool for the study of this activity in a nerve cell.