Percutaneous antegrade pyelography should be considered in the few, select, critically ill newborns with bilateral renal cystic disease when the diagnosis is critical to management and difficult with the usual imaging procedures. Two extremely ill newborns with severe oliguria and cystic abnormalities in both kidneys by ultrasound underwent sonographic guidance for percutaneous antegrade nephrostograms in the first week of life. With injection of contrast medium, definitive diagnoses were made of a multicystic dysplastic kidney on one side and an obstructed hydronephrotic kidney on the other, thereby directing decompression of the obstructed kidney to preserve native renal function. This procedure can provide a definitive diagnosis in these rare but difficult cases.