Hydroxystilbamidine bis(methanesulfonate), a dye capable of binding to both DNA and RNA, has been found to be a powerful inhibitor of cellular ribonucleases. In Vitro: It is found that the trypanocidal dye Hydroxystilbamidine bis(methanesulfonate) permits the recovery of mRNA after polysome released with Nonidet P-40 (NP-40). Sucrose gradient analysis of detergent-lysed postnuclear supernates is used to analyze the size distribution of NP-40-released polysomes. The heparin gradient shows some polyribosomes, whereas the Hydroxystilbamidine bis(methanesulfonate) gradient shows a remarkably large peak of very heavy polyribosomes. This peak is obtained reproducibly if Hydroxystilbamidine bis(methanesulfonate) is present before the addition of NP-40^[1]. In Vivo: Hydroxystilbamidine bis(methanesulfonate) is an effective suppressor of the plaque-forming cell (PFC) response when given before sheep erythrocytes (SRBC) stimulation. Hydroxystilbamidine bis(methanesulfonate) depresses the plaque response of the treated mice. Fewer PFC are observed in Hydroxystilbamidine bis(methanesulfonate)-treated mice throughout the experiment, but the level of suppression decreases with time. By day 14, the number of PFC observed in both the Hydroxystilbamidine bis(methanesulfonate) treated mice and the control group is essentially at the background level^[2].