This study was undertaken to determine whether the two type of cells (one neuroblast-like and the other epithelial in appearance) of the human neuroblastoma line SK-N-SH in culture undergo morphological interconversion, whether conversion is bidirectional, and whether there are coordinate neurochemical changes. Phenotypic analysis of serially isolated neuroblast clones (SH-SY, SH-SY5, SH-SY5Y) revealed conversion to epithelial-like cells. Conversely, conversion also was promoted from an epithelial-like clone (SH-EP) to neuroblastic subclones. Cell origin could be verified because of a marker chromosome specific to SH-EP. Only neuroblastic subclones of SH-EP contained activities for tyrosine hydroxylase and dopamine-beta-hydroxylase, enzymes unique to catecholamine neurons; epithelial-like cells lacked activities for these enzymes. These findings indicate a coordinate morphological and biochemical interconversion of neuroblastoma SK-N-SH cells and reveal a plasticity in phenotypic expression in malignant neuronal cells.