New boron-containing spermidine/spermine (SPD/SPM) analogues have been synthesized: N5-[4-(2-aminoethyl-o-carboranyl)butyl] and N5-{4-[(2,3-dihydroxypropyl)-o-carboranyl]butyl} SPD/SPM derivatives (ASPD-5, ASPM-5, DHSPD-5, and DHSPM-5) as well as N5-{[4-(dihydroxyboryl)phenyl]methyl}spermidine (BBSPD-5). These boronated polyamines retain their ability to displace ethidium bromide from calf thymus DNA and are rapidly taken up in vitro by F98 rat glioma cells. The in vitro toxicities of ASPD-5, ASPM-5, DHSPD-5, and DHSPM-5 are lower than those previously reported for N5-[4-(o-carboranyl)butyl] SPD/SPM derivatives (SPD-5 and SPM-5) but similar to those of native SPD and SPM. Very low toxicity was also observed for BBSPD-5. In vivo studies of ASPD-5 and BBSPD-5 were performed in mice bearing intracerebral implants of the GL261 glioma and subcutaneous implants of the B16 melanoma. The biodistribution data found in both tumor models suggest that the polyamines synthesized to date do not appear to be suitable boron agents for BNCT.