The dissipation and side-effect of metribuzin (MBZ) were studied with various factors; two soil types (clay loam and sandy loam), soil amendment (wheat straw and without amendment), two temperature levels (25 and 50°C), sterilization (sterilized and unsterilized soil) and time of incubation (15 and 30 days) and designed by Windows version of MINITAB software package to reduce the time and the cost as well as increased the precision. Determination of MBZ by HPLC with recoveries ranged from 50.85 to 108.09%. The MBZ residues were detected in all samples up to 60 days of storage, respectively with decline in their concentrations with the time of incubation. The clay loam soil showed higher dissipation than the sandy loam soil. The different factors in the present study confirmed that the wheat straw amendment, non-sterilization and incubation at 50°C caused higher dissipation of MBZ than without wheat straw, sterilization and incubation at 25°C. The dissipation was described mathematically by a first order equation with t0.5 was ranged from 9.62 to 16.82 days in clay loam soil and from 10.01 to 16.04 days in sandy loam soil. The side-effect of MBZ was tested on soil dehydrogenase activity that can be considered as an indicator of the biological activity and microbial degradation. The result proved that the enzyme activity was significantly decreased in all treatments compared with the controls at 1 and 3 days of incubation then it was gradually increased at 7, 10, 15 and 30 days of incubation. Treatments of wheat straw, non-sterilized and incubated at 25°C or 50°C showed the lowest enzyme inhibition among all treatments.