The possibility that one or both of the synthetic triarnines, 1,3,6-triarninohexane and 1,4,7-triarninoheptane, could substitute for the naturally occurring polyarnines in the growth of SV-3T3 cells was investigated. It was found that these triarnines did lead to a restoration of growth in cells in which sperrnidine content had been depleted by exposure to the ornithine decarboxylase inhibitor 2-difluoromethylornithine. This resumption of a normal growth rate occurred prior to the reduction in the content of cellular decarboxylated Sadenosylrnethionine, suggesting that this nucleoside (which increases in concentration several hundred-fold in cells treated with 2-difluorornethylornithine) does not cause the reduction of cell growth. However, unlike t h e increase in cell growth brought about by sperrnidine, which continued indefinitely, the increase produced by 1,3,6-triarninohexane or 1,4,7-triarninoheptane was transient. Cell growth in the presence of 2-difluorornethylornithine and these triarnines stopped after about three or four population doublings. This corresponded to the time at which the intracellular sperrnine content of the cells was reduced to values less than 20% of normal. It is suggested that the increased growth rate of sperrnidine-depleted cells in response to these triarnines is due to their uptake into the cell and ability to displace sperrnine from intracellular sites, thus making sperrnine available to fulfill the polyamine function($ essential for growth. These results indicate that the naturally occurring polyarnines sperrnidine or sperrnine are essential for continued cell growth and cannot be replaced by analogues containing only primary amino groups.