BACKGROUND A fluorine substituted derivative of meta-iodobenzylguanidine (MIBG), 4-fluoro-3-iodobenzylguanidine (FIBG), is retained in SK-N-SH human neuroblastoma cells in vitro to a higher degree than the MIBG. METHODS To investigate whether the higher retention of FIBG is due to differences in the catabolic degradation of the two tracers, in vitro paired-label studies were performed using SK-N-SH cells. RESULTS No detectable amount of benzyl amines, benzoic acids or hippuran derivatives, potential catabolites of these tracers, were seen in either case. Even after 48 h, the cell culture supernatants contained exclusively intact I-MIBG and I-FIBG. In contrast, in some cases, HPLC analysis of cell lysates indicated the presence of a very polar compound(s) as the predominant species with smaller quantities of intact tracers. The per cent total radioactivity in the lysate at each time point that was associated with intact I-FIBG was (average [range]) 25.4% [20.3-30.5], 22.5% [19.3-25.6], and 18.8% [14.3-23.3], at 0 h, 24 h and 48 h, respectively. The corresponding values for I-MIBG were 24.3% [21.0-27.5], 19.1% [11.7-26.5] and 17.4% [14.6-20.1]. No significant amount of activity was associated with high molecular weight species for either halobenzylguanidine, indicating that protein binding was not a major factor.