The use of buckminsterfullerene (C-60) carbon clusters as a matrix for MALDI-TOFMS of uranium determination was studied. The C-60 fullerene is easily ionized either to C-60(-) or C-60(+) ions and when increasing the laser energy, the destruction of C-60 to C-58,C- C-56, C-54, etc. fragments and the formation of higher carbon clusters C-106(+), C-108(+), C-118(+), etc. is observed. In the same time with the fullerene destruction, the intensity of uranium oxide peaks UO2+ and UO+ is intensified. Conditions such as laser energy and the use of linear, reflectron, negative or positive modes were studied and the detection limit of uranium down to similar to50 femto mol of uranium was reached.