The behaviour is not interactive mode specific...

#!/usr/bin/perl -w

use strict;

print "Setting \@Foo::ISA = ()\n";
@Foo::ISA = ();
print "UNIVERSAL::isa( 'Foo', 'UNIVERSAL' ) == '" . UNIVERSAL::isa( 'F
+oo', 'UNIVERSAL' ) . "'\n";
print "UNIVERSAL::isa( 'Foo', 'UNIVERSAL' ) == '" . UNIVERSAL::isa( 'F
+oo', 'UNIVERSAL' ) . "'\n";
print "UNIVERSAL::isa( 'Foo', 'UNIVERSAL' ) == '" . UNIVERSAL::isa( 'F
+oo', 'UNIVERSAL' ) . "'\n";
exit();

... resulting in ...

Setting @Foo::ISA = ()
UNIVERSAL::isa( 'Foo', 'UNIVERSAL' ) == '1'
UNIVERSAL::isa( 'Foo', 'UNIVERSAL' ) == ''
UNIVERSAL::isa( 'Foo', 'UNIVERSAL' ) == ''
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On the other matter, I'm aware things work slightly differently in the debugger, but I use it for things like the 'x' command and other stuff...