Heat shock promoters have been employed to achieve tightly regulated expression of transformed genes in a wide variety of model systems including tissue culture cells, bacteria, yeast, Drosophila, and more recently Caenorhabditis elegans. Here we investigate the feasibility of using a laser microbeam to induce a sub-lethal heat shock response in individual cells of C. elegans. We demonstrate that in transgenic strains carrying heat shock promoter-lacZ fusions, single cell expression of β-galactosidase in a variety of cell types of endodermal, mesodermal, or ectodermal origin can be achieved after pulsing with a laser. A tissue-general, inducible promoter can therefore be converted into one of single cell specificity which can be induced rapidly at any point in development, offering unique opportunities to study cell-cell interactions in C. elegans. This technique defines a new approach to generate mosaic animals and may be adaptable to other organisms or tissues. © 1993 Wiley-Liss, Inc.