Studies of quantitative changes in gene expression in malignant cells have often used housekeeping genes as controls against which the level of expression of a gene under study could be compared. We have now examined whether the expression of the most commonly used of these housekeeping genes can be regarded as reliable controls for gene expression studies in non-Hodgkin's lymphoma (NHL). We have used Northern blot analysis to compare the levels of expression of beta-actin, alpha-tubulin, beta 2-microglobulin and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) to that of ribosomal RNA. These studies demonstrated that whereas there was a reasonable correlation between the relative levels of rRNA and housekeeping gene expression in reactive hyperplastic nodes, there were major differences in the relative levels of expression of the housekeeping genes in both low and high grade lymphomas; only GAPDH showed any degree of consistency. These observations indicated that housekeeping gene expression was not a reliable control for estimating changes in the level of expression of other genes in NHL, and instead suggested that 18S or 28S rRNA expression offered a more accurate method of RNA quantitation.